JP2948254B2 - Anti-adhesion material - Google Patents

Anti-adhesion material

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Publication number
JP2948254B2
JP2948254B2 JP2056021A JP5602190A JP2948254B2 JP 2948254 B2 JP2948254 B2 JP 2948254B2 JP 2056021 A JP2056021 A JP 2056021A JP 5602190 A JP5602190 A JP 5602190A JP 2948254 B2 JP2948254 B2 JP 2948254B2
Authority
JP
Japan
Prior art keywords
chitin
adhesion
chitosan
solution
present
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
JP2056021A
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Japanese (ja)
Other versions
JPH03258723A (en
Inventor
紘爾 木船
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
YUNICHIKA KK
Original Assignee
YUNICHIKA KK
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Priority to JP2056021A priority Critical patent/JP2948254B2/en
Publication of JPH03258723A publication Critical patent/JPH03258723A/en
Application granted granted Critical
Publication of JP2948254B2 publication Critical patent/JP2948254B2/en
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Expired - Lifetime legal-status Critical Current

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Description

【発明の詳細な説明】 (産業上の利用分野) 本発明は,キチンからなる癒着防止材に関するもので
あり、特に医療分野における外科的手術後等に生体修復
の過程において発生する生体組織間の癒着防止に好適な
癒着防止材に関するものである。
Description: TECHNICAL FIELD The present invention relates to an anti-adhesion material composed of chitin, and more particularly to a method for repairing biological tissue generated during a biological repair process after a surgical operation in the medical field. The present invention relates to an adhesion preventing material suitable for preventing adhesion.

(従来の技術) 一般に生体組織は,欠損が起こった場合,生体の修復
の過程において,欠損した組織が他の欠損したものまた
は正常な組織と癒着することはよく知られている。特
に,体内の外科的手術後は癒着が非常に発生しやすい状
態にある。この癒着は,しばしば臓器の正常な運動を妨
げることになり,最悪の場合,生命をおびやかす原因と
なることがある。
(Prior Art) In general, it is well known that when a defect occurs in a living tissue, the defective tissue adheres to another defective or normal tissue in the process of repairing the living body. In particular, adhesions are very likely to occur after internal surgery. This adhesion often interferes with the normal movement of the organ and, at worst, can be life-threatening.

その対策として,従来は外科手術の際,例えば,切開
面の縫合の際に縫合面に露出させないように工夫した
り,植物油や動物油を患部に塗布したり,患部に布やフ
イルムをあてたりして癒着を防止する方法がとられてい
た。
As a countermeasure, conventionally, during surgery, for example, when suturing the incision surface, it is necessary to devise it so that it is not exposed to the suture surface, apply vegetable oil or animal oil to the affected area, or apply cloth or film to the affected area. To prevent adhesions.

(発明が解決しようとする課題) しかし,このような対策には限界があった。すなわ
ち,手術時の外科的手法をいかに工夫しても,やはり癒
着はしばしば発生したし,植物油や動物油を患部に塗布
しても,これらは生体液等で脱離しやすく,十分な効果
が得られない場合が多かった。患部に布やフイルムをあ
てる場合も,生体親和性がよく,かつ異物反応のない材
料であることが望ましいが,このような材料は限られて
おり,未だ生体吸収性,生体親和性のあるもので実用化
されているものはなかった。
(Problems to be solved by the invention) However, such measures have limitations. In other words, no matter how the surgical technique is devised during surgery, adhesion often occurs, and even if vegetable or animal oils are applied to the affected area, they can be easily detached with biological fluids, etc., and sufficient effects can be obtained. Often not. When a cloth or film is applied to the affected area, it is desirable that the material has good biocompatibility and does not react with foreign substances. However, such materials are limited and those that are still bioabsorbable and biocompatible. Nothing has been put to practical use.

本発明は,生体の創,切開面または外科的手術後にお
いて癒着を良好に防止し,生体に異常な反応を起こさ
ず,かつ経時後には消失する生体吸収性を有する癒着防
止材を提供することを目的とするものである。
An object of the present invention is to provide an anti-adhesion material having a bioabsorbable property that prevents adhesions favorably after wounds, incisions or surgical operations on a living body, does not cause an abnormal reaction in the living body, and disappears over time. It is intended for.

(課題を解決するための手段) 本発明者は,上記の目的を達成するため鋭意研究を重
ねた結果,キチンがかかる課題を達成できることを見出
し,本発明に到達したものである。
(Means for Solving the Problems) The present inventors have made intensive studies to achieve the above object, and as a result, have found that chitin can achieve such problems, and have reached the present invention.

すなわち,本発明は,キチンからなる癒着防止材を要
旨とするものである。
That is, the present invention has as its gist an anti-adhesion material comprising chitin.

以下,本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.

キチンとは,甲殻類,昆虫類等の外骨格を塩酸処理並
びに苛性ソーダ処理し,灰分および蛋白質を除去して得
られるポリ(N−アセチル−D−グルコサミン)または
このポリ(N−アセチル−D−グルコサミン)をアルカ
リで処理して得られる脱アセチル化物(脱アセチル化度
で数%から100%までの値のものがある)であり、これ
らのうち,脱アセチル化度が高く,酸に溶解するものを
特にキトサンと呼んでいる。
Chitin refers to poly (N-acetyl-D-glucosamine) obtained by treating exoskeletons of crustaceans and insects with hydrochloric acid and caustic soda to remove ash and proteins, or poly (N-acetyl-D-glucoseamine). Glucosamine) is a deacetylated product obtained by treating it with an alkali (the degree of deacetylation varies from several percent to 100%). Of these, the degree of deacetylation is high and it is soluble in acids. Things are especially called chitosan.

本発明で用いられるキチンは,このようなキチンある
いはキトサンであり,さらには,キチンあるいはキトサ
ンのグルコサミン残基の−OH基,−CH2OH基,−NH2基,
あるいは−NHCOCH3基が他の基で置換されたもの,例え
ばエステル化,エーテル化,カルボキシメチル化,ヒド
ロキシエチル化あるいはo−エチル化されたもの等の誘
導体も含まれる。
Chitin used in the present invention is such a chitin or chitosan, and further, -OH groups of glucosamine residues of chitin or chitosan, -CH 2 OH group, -NH 2 group,
Alternatively, a derivative in which the —NHCOCH 3 group is substituted with another group, for example, an esterified, etherified, carboxymethylated, hydroxyethylated or o-ethylated derivative is also included.

キチンの脱アセチル化はキチンをアルカリ処理すると
いう周知の方法により行うことができる。この際使用す
るアルカリ濃度,処理温度あるいは処理時間等を適宜変
えることによって脱アセチル化度を容易に調整すること
ができる。
Deacetylation of chitin can be performed by a well-known method of treating chitin with an alkali. At this time, the degree of deacetylation can be easily adjusted by appropriately changing the alkali concentration, the treatment temperature or the treatment time used.

本発明で用いられるキチンの脱アセチル化度は特に制
限されるものではない。
The degree of deacetylation of chitin used in the present invention is not particularly limited.

本発明の癒着防止材は,上記したキチンからなるもの
であるが,その形態としては,粉末,水溶液,綿状体,
フイルム,不織布,編織布,多孔体等種々のものがあ
る。
The anti-adhesion material of the present invention comprises the above-described chitin, and may be in the form of a powder, an aqueous solution, a floc,
There are various types such as a film, a nonwoven fabric, a woven fabric, and a porous body.

本発明の粉末状の癒着防止材は,精製されたキチンを
用い,粉砕機によって粉砕して得ることができ,粉末状
キチンの粒度としては,細かいものがよく,例えば100
メツシユ以上のものが好ましい。
The powdery anti-adhesion material of the present invention can be obtained by using a purified chitin and pulverizing with a pulverizer. The fine particle size of the powdery chitin is preferably, for example, 100%.
Mesh or higher is preferred.

本発明の溶液状の癒着防止材は,水溶性キチン(例ば
キトサンやカルボキシメチルキチン)を水あるいは酢酸
の水溶液に溶かして作成することができ,水溶性キチン
の濃度としては,0.5〜5重量%程度が好ましい。
The solution-based anti-adhesion material of the present invention can be prepared by dissolving water-soluble chitin (eg, chitosan or carboxymethyl chitin) in water or an aqueous solution of acetic acid. The concentration of water-soluble chitin is 0.5 to 5% by weight. % Is preferable.

本発明の綿状体,フイルム,不織布,編織布,多孔体
等の癒着防止材は周知の湿式法で成形することができ
る。すなわち,成形体を得るには,キチンを溶剤に溶か
して溶液とし,それを非溶剤である凝固液によって凝固
すればよい。溶剤は,キチンの化学的構造によって好適
のものを選ぶことができる。例えば,脱アセチル化度の
低いポリ(N−アセチル−D−グルコサミン)の場合,
トリクロル酢酸と塩素化炭化水素との混合物,ジメチル
アセトアミドまたはN−メチルピロリドンと塩化リチウ
ムとの混合物等が用いられ,脱アセチル化度の高いキト
サンの場合,酢酸等の酸水溶液が用いられる。また、凝
固液としては,水,アルコール,ケトン類等が用いられ
る。フイルム,多孔体については,一時に湿式成形可能
だが,綿状体,不織布,編織布については,まず,キチ
ン繊維を製造した後,常法によって作成することができ
る。これらの成形品の製造法は,“キチン,キトサンの
応用”(技報堂出版,p99,1990年)等に記載されてい
る。
The adhesion preventing material of the present invention, such as a flocculent body, a film, a nonwoven fabric, a woven fabric, and a porous body, can be formed by a well-known wet method. That is, in order to obtain a molded body, chitin may be dissolved in a solvent to form a solution, which is then coagulated with a non-solvent coagulating liquid. A suitable solvent can be selected depending on the chemical structure of chitin. For example, in the case of poly (N-acetyl-D-glucosamine) having a low degree of deacetylation,
A mixture of trichloroacetic acid and a chlorinated hydrocarbon, a mixture of dimethylacetamide or N-methylpyrrolidone and lithium chloride, and the like are used. In the case of chitosan having a high degree of deacetylation, an aqueous acid solution such as acetic acid is used. Water, alcohol, ketones and the like are used as the coagulating liquid. Films and porous bodies can be wet-molded at a time, but cotton-like bodies, non-woven fabrics and woven fabrics can be prepared by first producing chitin fibers and then using conventional methods. The production method of these molded articles is described in “Application of chitin and chitosan” (Gihodo Shuppan, p99, 1990) and the like.

これらの本発明の種々の形状の癒着防止材は,通常外
科的手術に伴う癒着防止材として使用することができ,
主として生体内,例えば,食道,胃,小腸,大腸,胆の
う,膵臓,肝臓,腎臓,心臓,腹膜,子宮,膀胱等の内
蔵器の切開,縫合,修復手術等の際に患部に付与すれば
よい。粉末,水溶液の場合は患部に塗布し,フイルム,
不織布,繊維布等の場合は患部にパツチ材としてあて,
他の臓器等と隔離するようにして使用することができ
る。癒着防止の効果が必要な期間中にパツチ材が移動す
るのを防ぐため,縫合糸等で患部に縫付けると特に効果
的である。
These anti-adhesion materials of various shapes according to the present invention can be used as anti-adhesion materials usually associated with surgical operations.
It may be given to the affected area mainly in the body, for example, at the time of incision, suturing, repair surgery, etc. of internal organs such as esophagus, stomach, small intestine, large intestine, gall bladder, pancreas, liver, kidney, heart, peritoneum, uterus, and bladder . In the case of powder or aqueous solution, apply to the affected area,
In the case of non-woven fabric, fiber cloth, etc., apply it to the affected area as a patch.
It can be used so as to be isolated from other organs. It is particularly effective to sew the patch with a suture or the like on the affected area to prevent the patch material from moving during the period in which the effect of preventing adhesion is required.

本発明の癒着防止材は,使用後,患部が他の臓器等に
癒着しないという効果があるとともに,患部の治療が終
了した後に生分解して消失するものである。この分解は
生体内酵素によって行われ,主な酵素としては,リゾチ
ーム,β−N−アセチル−グルコサミンダーゼ等であ
る。生分解されるに要する時間としては,癒着防止材と
しての形状によって異なるが,通常は3〜5ヵ月であ
る。
The anti-adhesion material of the present invention has an effect that the affected part does not adhere to other organs or the like after use, and is biodegradable and disappears after the treatment of the affected part is completed. This decomposition is carried out by in vivo enzymes, and the main enzymes are lysozyme, β-N-acetyl-glucosamidase and the like. The time required for biodegradation depends on the shape of the adhesion preventing material, but is usually 3 to 5 months.

(実施例) 以下,本発明を実施例によってさらに具体的に説明す
る。
(Examples) Hereinafter, the present invention will be described more specifically with reference to examples.

実施例1 白色キチン粉末(脱アセチル化度2.5%,ジメチルア
セトアミド:塩化リチウム=9/1の溶液に0.1w/w%溶解
した時の溶液の溶液粘度220センチポイズ,新日本化学
株式会社製)をジメチルアセトアミドと塩化リチウムの
混合溶液(重量比9:1)に常温で9w/w%溶解し,透明の
粘調な溶液を作成した。この溶液を2000メツシュステン
レスネツトにて濾過した後,減圧脱泡を行い,ギヤーポ
ンプにて輸送して,ノズルから80℃の水中に吐出するこ
とにより湿式紡糸を行った。吐出された糸条は,10m/min
の速度でボビンで巻取り,150デニール50フイラメントの
長繊維を得た。得られた長繊維は,強度3.5g/d,伸度12.
4%であった。
Example 1 White chitin powder (deacetylation degree: 2.5%, dimethylacetamide: solution of 0.1 w / w% in a solution of lithium chloride = 9/1, solution viscosity of the solution: 220 centipoise, manufactured by Shin Nippon Chemical Co., Ltd.) 9 w / w% was dissolved in a mixed solution of dimethylacetamide and lithium chloride (weight ratio 9: 1) at room temperature to prepare a transparent viscous solution. This solution was filtered through a 2000 mesh stainless steel net, degassed under reduced pressure, transported by a gear pump, and discharged from a nozzle into water at 80 ° C. to perform wet spinning. The discharged yarn is 10m / min
The filament was wound on a bobbin at a speed of 150 denier and 50 filaments. The obtained long fiber has a strength of 3.5 g / d and an elongation of 12.
4%.

得られた長繊維を丸編機(小池機械製作所製,CR−B
型)にて丸編みにし,その布を10cm×10cmの大きさに切
断してエチレンオキシドガスにて滅菌した。一方,家兎
を麻酔した後開腹し,胃を取り出して2cmの巾で2ヶ所
切開した後,ポリエステル縫合糸でそれぞれを縫合し,
一方の切開創には本発明のキチン布をあて,四方をポリ
エステル縫合糸で簡単に固定した。他の創はそのままに
して,再度ポリエステル縫合糸で閉腹した。
The obtained long fiber is transferred to a circular knitting machine (Koike Kikai Seisakusho, CR-B
The cloth was cut into a size of 10 cm × 10 cm and sterilized with ethylene oxide gas. On the other hand, the rabbit was anesthetized and laparotomy was performed, the stomach was removed, and two incisions were made at a width of 2 cm, and each was sewn with polyester suture.
One incision was applied with the chitin cloth of the present invention, and the four sides were easily fixed with polyester sutures. The other wounds were left as they were, and the abdomen was closed again with polyester suture.

10日後,再度開腹して胃の切開部を観察したところ,
キチン布をあてた創には他臓器等の癒着は全くなかった
のに対し,あてなかった創には小腸,肝臓が強い結合組
織を介して癒着していた。
Ten days later, the abdomen was reopened and the incision in the stomach was observed.
Wounds applied with chitin cloth did not have any adhesions to other organs, whereas wounds not applied had adhesions of the small intestine and liver through strong connective tissue.

実施例2 キトサン粉末(脱アセチル化度85%,0.2%酢酸水溶液
に溶解した後の溶解粘度が580センチポイズ,新日本化
学製)を0.4%酢酸水溶液に1w/w%溶かしてキトサン溶
液を作った。一方,家兎を麻酔し,腹部に長さ50cmの切
開創を作り,いずれも腹膜まで完全に切開した。その一
方の創の部分には,体液を除去しながら上記キトサン溶
液を腹膜に至るまで十分に塗布した。塗布後,創はポリ
エステル縫合糸で縫合し,再度上部からキトサン溶液を
塗布した。他の創はそのままポリエステル縫合糸で縫合
した。
Example 2 A chitosan solution was prepared by dissolving chitosan powder (deacetylation degree: 85%, dissolution viscosity after dissolving in 0.2% acetic acid aqueous solution, 580 centipoise, manufactured by Shin Nippon Chemical) at 1% w / w% in 0.4% acetic acid aqueous solution. . On the other hand, a rabbit was anesthetized, and an incision of 50 cm in length was made in the abdomen. The chitosan solution was sufficiently applied to the one wound so as to reach the peritoneum while removing the body fluid. After application, the wound was sutured with a polyester suture, and the chitosan solution was applied again from above. Other wounds were directly sewn with polyester suture.

1週間後,家兎を屠殺して調べたところ,キトサン溶
液を塗布した創部には内側から胃,小腸等の癒着が全く
観察されなかったのに対し,塗布しなかった創部には強
い癒着および結合組織の癒着が認められた。
One week later, the rabbits were sacrificed and examined. No adhesion of the stomach, small intestine, etc. was observed from the inside of the wound to which the chitosan solution was applied, whereas strong adhesion and non-adhesion were observed to the wound without application. Adhesion of connective tissue was observed.

実施例3 キトサン粉末(脱アセチル化度88%,0.2%酢酸水溶液
に溶解した後の溶解粘度が894センチポイズ,新日本化
学製)を1%酢酸水溶液に2w/w%溶かしてキトサン溶液
を作った。これをガラスプレート上に1mmの厚さに流延
して70℃の熱風乾燥器で2時間熱処理したところ,厚さ
52μmのキトサンフイルムが得られた。一方,雑種成犬
を麻酔して開腹し,小腸を取り出した。この小腸の2ヵ
所を輪切りに切断し,それぞれ全周をポリプロピレン製
縫合糸で縫合して修復した。縫合後,一方は全周にキト
サンフイルムを巻付け,小腸壁に縫合糸で軽く固定し
た。他の一方はそのままにして閉腹した。
Example 3 A chitosan solution was prepared by dissolving chitosan powder (deacetylation degree: 88%, dissolution viscosity after dissolving in 0.2% acetic acid aqueous solution, 894 centipoise, manufactured by Shin Nippon Chemical) at 2% w / w% in 1% acetic acid aqueous solution. . This was cast on a glass plate to a thickness of 1 mm and heat-treated in a hot air dryer at 70 ° C for 2 hours.
A 52 μm chitosan film was obtained. Meanwhile, the adult mongrel dog was anesthetized and laparotomy was performed, and the small intestine was removed. Two portions of the small intestine were cut into slices, and the entire circumference was repaired by suturing with a suture made of polypropylene. After suturing, one side was wrapped with chitosan film around the entire circumference and lightly fixed to the small intestinal wall with a suture. The other was left closed.

犬は手術前と同じ食料で飼育し,15日後,屠殺して小
腸を観察したところ,キトサンフイルムを巻付けた箇所
には他臓器の癒着が全くみられなかったのに対し,キト
サンフイルムを巻付けなかった箇所については,胃,肝
臓,膵臓および結合組織の強い癒着が観察された。
The dogs were bred on the same food as before surgery and were sacrificed 15 days later, and the small intestine was observed. As a result, no adhesion of other organs was found at the area where the chitosan film was wrapped, whereas the chitosan film was wrapped. In the areas not attached, strong adhesion of the stomach, liver, pancreas and connective tissue was observed.

(発明の効果) 本発明の癒着防止材は,生体内の特に外科的手術によ
って発生した創が手術後に癒着することを防止できるも
ので,また,生体との異物反応が小さく,かつ生体吸収
性があり,役目が終了した後に消失し,生体内に異物と
しての残存のないものである。したがって,再手術後も
勿論必要ではなく,正常な患部の修復に有用である。
(Effect of the Invention) The anti-adhesion material of the present invention can prevent wounds generated in a living body, particularly by a surgical operation, from adhering after surgery, have a small foreign body reaction with the living body, and have a bioabsorbable property. It disappears after the end of its role and does not remain as a foreign substance in the living body. Therefore, it is not necessary even after reoperation, and is useful for repairing a normal affected part.

Claims (1)

(57)【特許請求の範囲】(57) [Claims] 【請求項1】キチンからなる癒着防止材。An anti-adhesion material comprising chitin.
JP2056021A 1990-03-06 1990-03-06 Anti-adhesion material Expired - Lifetime JP2948254B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2056021A JP2948254B2 (en) 1990-03-06 1990-03-06 Anti-adhesion material

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2056021A JP2948254B2 (en) 1990-03-06 1990-03-06 Anti-adhesion material

Publications (2)

Publication Number Publication Date
JPH03258723A JPH03258723A (en) 1991-11-19
JP2948254B2 true JP2948254B2 (en) 1999-09-13

Family

ID=13015410

Family Applications (1)

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US9155751B2 (en) 2005-06-08 2015-10-13 The University Of Tokyo Solution for tissue adhesion prevention and method for tissue adhesion prevention

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FR2848118B1 (en) * 2002-12-06 2006-08-11 Textile Hi Tec PROTHESIS COMPOSITE
GB0909136D0 (en) 2009-05-28 2009-07-01 Profibrix Bv Dry powder composition
WO2010136588A2 (en) 2009-05-28 2010-12-02 Profibrix B.V. Dry powder fibrin sealant

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9155751B2 (en) 2005-06-08 2015-10-13 The University Of Tokyo Solution for tissue adhesion prevention and method for tissue adhesion prevention

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